Synthesis and Cytotoxicity Evaluation of Some Novel Thiazoles, Thiadiazoles, and Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones Incorporating Triazole Moiety

Abstract

Abstract:Reactions of hydrazonoyl halides and each of methyl 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbodithioate and 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbothioamide afforded 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-3-phenyl-5-substituted-2,3-dihydro-1,3,4-thiadiazoles and 5-(4-substituted)diazenyl)-2-(2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-arylthiazoles, respectively. Analogously, the reactions of hydrazonoyl halides with 7-1H)-ones in a good yield. The structures of the newly synthesized were elucidated via elemental analysis, spectral data and alternative synthesis routes whenever possible. Twelve of the newly synthesized compounds have been evaluated for their antitumor activity against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (HepG2) cell lines. Their structure activity relationships (SAR) were also studied. The 1,3,4-thiadiazole derivative 9b (IC50 = 2.94 µM) has promising antitumor activity against the human hepatocellular carcinoma cell line and the thiazole derivative 12a has promising inhibitory activity against both the human hepatocellular carcinoma cell line and the breast carcinoma cell line (IC50 = 1.19, and 3.4 µM, respectively).

A Decade of Development of Ethylidenethiosemicarbazides as Building Blocks for Synthesis of Azoles and Azines (A Review)

“…The biological activity of ethylidenethiosemicarbazides is related to their chelating ability with metal ion through either thione or thiolate sulfur and one of the hydrazone-nitrogen atoms 12 . Furthermore, ethylidenethiosemicarbazides have been used as a reactive building blocks for synthesis of different azoles such as, bis-thiazoles 13 , [1,3,4]thiadiazoles 14 , [1,3,4]oxadiazoles 15 , thiazolidin-4-ones 16 , imidazolinones 17 , and thiazoles 18,19 . In this survey, we represent three approaches about ethylidenethiosemicarbazides, with different aryl or heterocyclic moieties, including synthesis, reactivity, and their biological activities.…”

Synthesis of Certain New Thiazole and 1,3,4‐Thiadiazole Derivatives via the Utility of 3‐Acetylindole

“…Other compounds derived from 3‐acetylindole are used in the treatment of gastrointestinal disorder , are useful as antiproliferative and potential antiviral agents , are used in the treatment of cardiovascular and central nervous system disorders , and are also used as herpes simplex type 1 integrase inhibitors . Encouraged by these observations and in continuation of our previous work in the synthesis of biologically active heterocycles , we synthesized newer heterocyclic indole derivatives with the hope to obtain better antiviral agents.…”

Synthesis of some new Pyridine‐based Heterocyclic Compounds with Anticipated Antitumor Activity

“…In the last decade, many researchers have reported a large series of pyrazole derivatives having promising anticancer activities , indicating the use of pyrazole motif as a powerful tool for novel anticancer drug development. Moreover, the 1,2,4‐triazolopyrimidines have also attracted growing interest due to their important pharmacological activities, such as antitumor potency, antimalarial, antimicrobial, anti‐inflammatory, antifungal, and macrophage activation .…”